The long-range aim of this research is the development of a unified theory of genetic control that incorporates both nuclear and cytoplasmic genetic systems. For this purpose we are using the unicellular eukaryote Chlamydomonas, an organism with both chloroplast and mitochondral genomes, as a model system. One specific aim is to quantitate genetic mapping procedures for the chloroplast genome on the basis of regularities in segregation and recombination of chloroplast genes that we previously established; and to develop analogous procedures for mitochondrial genes that we have recently begun to identify. A second aim is to investigate mutagenesis of organelle genes, both the molecular basis and the intracellular mechanisms responible for selection and expression of mutant genes when the organelle genome is multiploid. A third aim is to study the regulatory functions of organelle DNAs by examining the molecular basis of a process we previously described: the inhibition of nuclear DNA replication by antibiotics that block organelle protein synthesis while chloroplast and mitochondrial DNA synthesis continues. We plan now to find out whether initiation or elongation of nuclear DNA is prrmarily inhibited. A further aim is to investigate the role of modification and restriction ensymes in the regulation of non-Mendelian inheritance of organelle DNAs, and to use restriction endonucleases that cleave chloroplast DNA at specific sites to examine the physical arrangement of reiterated and single copy cmponents of DNA.